Abnormal Plasma Levels of Steroids and Their Ratios in Patients With Prurigo Nodularis: A Pilot Study

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients.Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity.Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores.Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity.Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

The adherence assessment based on the combination of nevirapine (NVP) and its two metabolites (2-hydroxynevirapine and 3-hydroxynevirapine) would more comprehensively and accurately reflect long-term adherence than that of a single prototype. This study aimed to develop a specific, sensitive and selective method for simultaneous detection of the three compounds in hair and explore whether there was consistency among the three compounds in assessing long-term adherence. Furthermore, 75 HIV-positive patients who were taking the NVP drug were randomly recruited and divided into two groups (high-and low-adherence group). All participants self-reported their days of oral drug administration per month and provided their hair strands closest to the scalp at the region of posterior vertex. The concentrations of three compounds in the hair were determined using a developed LC-MS/MS method in multiple reaction monitoring. This method showed good performances in limit of quantification and accuracy with the recoveries from 85 to 115% and in precision with the intra-day and inter-day coefficients of variation within 15% for the three compounds. The population analysis revealed that patients with high-adherence showed significantly higher concentrations than those with low-adherence for all three compounds. There were significantly moderate correlations of nevirapine with 2-hydroxynevirapine and 3-hydroxynevirapin and high correlation between 2-hydroxynevirapine and 3-hydroxynevirapin. The two NVP’s metabolites showed high consistency with NVP in evaluating long-term adherence

Hair Zidovudine Concentrations Predict Virologic Outcomes Among People Living with HIV/AIDS in China

Background: Hair antiretroviral concentrations are an objective and non-invasive measure of adherence to long-term antiretroviral therapy (ART) and can further predict virologic outcomes among people living with HIV/AIDS (PLWH). Zidovudine, one of the mainstream antiretrovirals in China, has been verified to have high reliability in adherence assessment, especially for its hair concentrations. However, data are limited in its predicting virologic outcomes. Therefore, this study aimed to characterize whether hair zidovudine concentrations can predict virologic suppression among Chinese PLWH compared with hair lamivudine concentrations and two self-reported measures, the overall frequency of adherence behaviors and percentage adherence. Methods: This cross-sectional study randomly recruited 564 PLWH currently treated with zidovudine, lamivudine, and other ART agents (efavirenz, nevirapine, or lopinavir/ritonavir) in Guangxi, China. Hair antiretroviral concentrations were determined using the LC-ESI+-MS/MS method. Receiver operating characteristic (ROC) curves were used to estimate the optimal classification thresholds of hair concentrations of zidovudine and lamivudine, and the two self-reported measures. Based on those optimal classification thresholds, logistic regression was used to examine whether those four adherence measures can predict virologic suppression (HIV-1 RNA \u3c 200 copies/mL). Results: ROC curves demonstrated good classification performance for association with virologic suppression of zidovudine with the optimal threshold at 58 pg/mg and lamivudine at 255 pg/mg but no self-reported measures. PLWH with hair zidovudine concentrations \u3e 58 pg/mg had an adjusted odds ratio (aOR) of 43.191 (95% confidence interval (CI) = 10.171‒183.418, p \u3c 0.001) for virologic suppression. Hair lamivudine concentrations were also associated with virologic suppression (aOR = 10.656, 95% CI = 3.670‒30.943, p \u3c 0.001). However, two self-reported measures did not predict virologic suppression (aORs = 1.157 and 2.488, ps \u3e 0.149). Conclusion: Hair zidovudine concentrations can be served as an alternative tool for clinically predicting virologic suppression among PLWH in China

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

The adherence assessment based on the combination of nevirapine (NVP) and its two metabolites (2-hydroxynevirapine and 3-hydroxynevirapine) would more comprehensively and accurately reflect long-term adherence than that of a single prototype. This study aimed to develop a specific, sensitive and selective method for simultaneous detection of the three compounds in hair and explore whether there was consistency among the three compounds in assessing long-term adherence. Furthermore, 75 HIV-positive patients who were taking the NVP drug were randomly recruited and divided into two groups (high-and low-adherence group). All participants self-reported their days of oral drug administration per month and provided their hair strands closest to the scalp at the region of posterior vertex. The concentrations of three compounds in the hair were determined using a developed LC-MS/MS method in multiple reaction monitoring. This method showed good performances in limit of quantification and accuracy with the recoveries from 85 to 115% and in precision with the intra-day and inter-day coefficients of variation within 15% for the three compounds. The population analysis revealed that patients with high-adherence showed significantly higher concentrations than those with low-adherence for all three compounds. There were significantly moderate correlations of nevirapine with 2-hydroxynevirapine and 3-hydroxynevirapin and high correlation between 2-hydroxynevirapine and 3-hydroxynevirapin. The two NVP’s metabolites showed high consistency with NVP in evaluating long-term adherence